The Food and Drug Administration approved two new indications for fam-trastuzumab deruxtecan-nxki (T-DXd; ENHERTU) on May 15, 2026, extending the antibody-drug conjugate’s regulatory footprint into early-stage HER2-positive breast cancer. The dual approval by AstraZeneca and Daiichi Sankyo covers neoadjuvant and post-neoadjuvant treatment settings, significantly broadening the drug’s label beyond its existing metastatic disease indications.

The first new approval allows T-DXd to be used as neoadjuvant therapy in adults with HER2-positive (IHC 3+ or ISH+) stage 2 or 3 breast cancer, administered prior to surgery followed by a taxane, trastuzumab, and pertuzumab (THP) regimen. The second covers post-neoadjuvant use in patients with residual invasive disease following prior HER2-targeted neoadjuvant therapy, a setting where patients historically faced limited options and poor prognosis.

The regulatory basis for the neoadjuvant indication is the DESTINY-Breast11 trial, which evaluated T-DXd followed by THP versus the established ddAC-THP regimen. The post-neoadjuvant approval was supported by DESTINY-Breast05, which compared T-DXd against trastuzumab emtansine (T-DM1) in patients with residual disease. In DESTINY-Breast05, T-DXd demonstrated statistically significant and clinically meaningful improvement in event-free survival over T-DM1 — itself the previous standard of care in this setting.

T-DXd is a HER2-directed monoclonal antibody (trastuzumab) conjugated via a cleavable tetrapeptide-based linker to a topoisomerase I inhibitor payload (DXd), with a drug-to-antibody ratio of approximately 8. The mechanism exploits HER2 receptor-mediated internalisation, releasing the cytotoxic payload intracellularly while a proportion diffuses across the cell membrane to exert a bystander killing effect on adjacent tumour cells — a feature that has proven clinically relevant in HER2-low and HER2-ultralow settings.

The FDA also approved two companion diagnostics alongside the indication: the PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody and the VENTANA HER2 Dual ISH DNA Probe Cocktail, to determine HER2 status in tumour specimens.

The prescribing information retains a boxed warning for interstitial lung disease and pneumonitis, which have been observed across T-DXd indications and require vigilant monitoring. Neutropenia and left ventricular dysfunction remain additional warnings and precautions.

With this approval, T-DXd now spans the HER2-positive breast cancer continuum from early-stage neoadjuvant through to heavily pre-treated metastatic disease. Market analysts project the early-stage expansion could add several billion dollars in annual peak sales. For smaller sponsors entering the HER2 space, the regulatory bar has materially shifted — partners with access to high-quality trial design and endpoint selection, like those at uniqtrials supporting ANZ-region HER2 studies, will be in high demand.